Phosphorylated HuR shuttles in cycles.
HuR is a ubiquitous RNA-binding protein (RBP) that associates with many mRNAs encoding proliferative proteins. Although predominantly nuclear, HuR translocation to the cytoplasm is linked to its ability to stabilize target mRNAs and modulate their translation. We recently reported that HuR phosphorylation by Cdk1 at S202 (within the HuR hinge region that is necessary for nucleocytoplasmic shuttle) increases HuR association with 14-3-3 and contributes to its nuclear retention. In the next issue of Cell Cycle we report that residue S242 also regulates HuR's cytoplasmic localization, influences cyclin expression, and modulates cell proliferation. Together with evidence of other post-translational HuR modifications, we propose that HuR phosphorylation ensures the timely mobilization of HuR across the nuclear envelope. In this manner, HuR helps to schedule gene expression programs in a cell cycle-dependent manner.
Kim
Hyeon Ho
HH
Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, Maryland 21224, USA.
Gorospe
Myriam
M
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000954:Antigens, Surface; D016213:Cyclins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016601:RNA-Binding Proteins; D011493:Protein Kinase C